Duan-Fang Shao1, Xiao-Hong Wang2, Zi-Yu Li1, Xiao-Fang Xing3, Xiao-Jing Cheng3, Ting Guo3, Hong Du3, Ying Hu2, Bin Dong4, Ning Ding1, Lin Li1, Shen Li1, Qing-Da Li1, Xian-Zi Wen3, Lian-Hai Zhang1, Jia-Fu Ji1. 1. Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing Cancer Hospital & Institute, Peking University School of Oncology Beijing, China. 2. The Tissue Bank, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing Cancer Hospital & Institute, Peking University School of Oncology Beijing, China. 3. Department of Gastrointestinal Translational Research, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing Cancer Hospital & Institute, Peking University School of Oncology Beijing, China. 4. Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing Cancer Hospital & Institute, Peking University School of Oncology Beijing, China.
Abstract
BACKGROUND: The SUMO pathway has been shown to play an important role in tumorigenesis. This report analyzed the involvement of the sole SUMO-Activating Enzyme Subunit 2 (SAE2) in human gastric cancer (GC) progression and prognosis. METHODS: Expression of SAE2 was examined by Quantigene Plex, western blotting and immunohistochemistry. The expression of SAE2 and c-MYC were detected in parallel in 276 cases. The molecular mechanisms of SAE2 expression and its effects on cell growth, colony formation, migration and invasion were also explored by CCK8 assay, colony formation experiment, transwell chamber assay with or without matrigel, immunoprecipitation and in vivo tumorigenesis and tumor metastasis. RESULTS: SAE2 was markedly overexpressed in GC cell lines and primary tumor samples of GC, and significantly correlated with deeper tumor depth, distant metastasis, higher pathological stage and stratified survival in human GC. SAE2 positivity was independently associated with a worse outcome in multivariate analysis. Knockdown of SAE2 expression inhibited the proliferation, migration, and invasion of SAE2-overexpressing GC cells. Consistent with the in vitro results, down-regulation of SAE2 in human GC BGC823 cells significantly reduced the tumorigenic and metastatic potential of the cells in vivo. SAE2 protein was significantly associated with the higher expression of c-MYC in primary GC tissues. Moreover, FoxM1 was SUMOylated in GC and that inhibition of SAE2 resulted in a decrease in SUMO1-FoxM1 levels compared with those in the controls. CONCLUSIONS: These findings suggest that SAE2 has a pivotal role in the aggressiveness of GC, and highlight its usefulness as a prognostic factor in GC.
BACKGROUND: The SUMO pathway has been shown to play an important role in tumorigenesis. This report analyzed the involvement of the sole SUMO-Activating Enzyme Subunit 2 (SAE2) in humangastric cancer (GC) progression and prognosis. METHODS: Expression of SAE2 was examined by Quantigene Plex, western blotting and immunohistochemistry. The expression of SAE2 and c-MYC were detected in parallel in 276 cases. The molecular mechanisms of SAE2 expression and its effects on cell growth, colony formation, migration and invasion were also explored by CCK8 assay, colony formation experiment, transwell chamber assay with or without matrigel, immunoprecipitation and in vivo tumorigenesis and tumor metastasis. RESULTS:SAE2 was markedly overexpressed in GC cell lines and primary tumor samples of GC, and significantly correlated with deeper tumor depth, distant metastasis, higher pathological stage and stratified survival in human GC. SAE2 positivity was independently associated with a worse outcome in multivariate analysis. Knockdown of SAE2 expression inhibited the proliferation, migration, and invasion of SAE2-overexpressing GC cells. Consistent with the in vitro results, down-regulation of SAE2 in human GC BGC823 cells significantly reduced the tumorigenic and metastatic potential of the cells in vivo. SAE2 protein was significantly associated with the higher expression of c-MYC in primary GC tissues. Moreover, FoxM1 was SUMOylated in GC and that inhibition of SAE2 resulted in a decrease in SUMO1-FoxM1 levels compared with those in the controls. CONCLUSIONS: These findings suggest that SAE2 has a pivotal role in the aggressiveness of GC, and highlight its usefulness as a prognostic factor in GC.
Authors: Joost Schimmel; Karolin Eifler; Jón Otti Sigurðsson; Sabine A G Cuijpers; Ivo A Hendriks; Matty Verlaan-de Vries; Christian D Kelstrup; Chiara Francavilla; René H Medema; Jesper V Olsen; Alfred C O Vertegaal Journal: Mol Cell Date: 2014-02-27 Impact factor: 17.970
Authors: Jessica D Kessler; Kristopher T Kahle; Tingting Sun; Kristen L Meerbrey; Michael R Schlabach; Earlene M Schmitt; Samuel O Skinner; Qikai Xu; Mamie Z Li; Zachary C Hartman; Mitchell Rao; Peng Yu; Rocio Dominguez-Vidana; Anthony C Liang; Nicole L Solimini; Ronald J Bernardi; Bing Yu; Tiffany Hsu; Ido Golding; Ji Luo; C Kent Osborne; Chad J Creighton; Susan G Hilsenbeck; Rachel Schiff; Chad A Shaw; Stephen J Elledge; Thomas F Westbrook Journal: Science Date: 2011-12-08 Impact factor: 47.728